Study Finds Lung Damage May Occur With Mild and Moderate COPD

Chronic obstructive pulmonary disease (COPD) is a chronic condition that damages the tissues of the lungs. Recent research has suggested that small airway disease is a pathological feature in mild and moderate COPD and that early intervention for disease modification may be required for those with mild or moderate COPD.

In scientific literature, it is well known that the main site of airflow obstruction in COPD is from small conducting airways; the last generation of small conducting airways, terminal bronchioles, are known to be destroyed in those with severe COPD. A study published in the Lancet aimed to determine whether destruction of the terminal and transitional bronchioles—the first generation of respiratory airways—occurs before or at the same time as emphysematous tissue destruction.

“The data suggest that the reason most clinical trials investigating COPD treatments in severe COPD did not show beneficial effects is because they were initiated after a substantial number of terminal and transitional bronchioles were already lost, and that early intervention in patients with mild and moderate COPD might be required for disease modification,” noted the researchers.

The researchers conducted a cross-sectional analysis by applying a novel multiresolution computed tomography imaging protocol to tissue samples from a uniform sampling method. Data were collected from representative unbiased samples of the whole lung or lobe of smokers with normal lung function (controls), patients with mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1), moderate COPD (GOLD 2), or very severe COPD (GOLD 4).

The patients with GOLD 1 or GOLD 2 COPD and smokers with normal lung function underwent lobectomy and pneumonectomy, whereas patients with GOLD 4 COPD underwent lung transplantation. Additionally, lung tissue samples were used for stereological assessment of the number and morphology of terminal and transitional bronchioles, airspace size, and alveolar surface area.

When the 34 patients (262 lung samples) in the study were compared with control smokers, the number of terminal bronchioles was lower by 40% in patients with GOLD 1 COPD and 43% in patients with GOLD 2 COPD. Also, the number of transitional bronchioles was 56% lower in those with GOLD 1 COPD and 59% lower in those with GOLD 2 COPD; the alveolar surface area was decreased by 33% and 45%, respectively. The researchers found a correlation between these pathological changes and lung function decline.

While there was significant loss of terminal and transitional bronchioles in lung samples from patients with GOLD 1 or GOLD 2 COPD that had a normal alveolar surface area, the remaining small airways had thickened walls and narrowed lumens, which are more obstructed with increasing GOLD stage COPD.

“This breakthrough finding will allow us to develop new drugs to treat patients with COPD at the earliest stages of their disease when the disease is reversible,” said Dr. Don Sin, the Canada Research Chair in COPD, in a press statement. “This will prevent disease progression in thousands of patients and help them stay out of the hospital and remain healthy in their own homes.”

Reference

Koo H-K, Vasilescu DM, Booth S, et al. Small airways disease in mild and moderate chronic obstructive pulmonary disease: a cross-sectional study [published online July 4, 2018]. Lancet. doi: 10.1016/S2213-2600(18)30196-6.